Study on critical-sized ultra-high molecular weight polyethylene wear particles loaded with alendronate sodium: in vitro release and cell response.

The aim of this study was to investigate the in vitro release and the effect of RAW 264.7 macrophages of critical-sized wear particles of ultra-high molecular weight polyethylene (UHMWPE) loaded with alendronate sodium (ALN), one of the most effective drugs to treat osteoporosis in clinic. The critical-sized UHMWPE-ALN 0.5 wt.% wear particles were prepared by vacuum gradient filtration combined with Pluronic F-68. In vitro release of ALN from critical-sized UHMWPE-ALN wear particles was investigated in phosphate buffered saline (PBS) at 37 °C with a shaker. Cell morphology, proliferation, lactate dehydrogenase (LDH) leakage and secretions of cytokines were evaluated after co-cultured with critical-sized UHMWPE-ALN wear particles in vitro. Results showed that ALN released from critical-sized UHMWPE-ALN wear particles included burst release and slow release in vitro. Macrophages would be chemotaxis and aggregated around the critical-sized UHMWPE-ALN or UHMWPE wear particle, which was phagocytosed with time. The proliferation of macrophages co-cultured with critical-sized UHMWPE-ALN wear particles was significantly decreased compared with that of critical-sized UHMWPE group. Meanwhile, the critical-sized UHMWPE-ALN wear particles significantly induced the LDH leakage of macrophages, which indicated the cell death. The death of macrophages induced by ALN was one of pathways to inhibit their proliferation. The secretions of cytokines (interleukin-6 and tumor necrosis factor-alpha) in critical-sized UHMWPE-ALN group were significantly lower than those in critical-sized UHMWPE group due to the released ALN. The present results suggested that UHMWPE-ALN had the potential application in clinic to treat osteolysis induced by wear particles.